tbuckley/cabot-search huggingface dataset:
Intraoperative radiation therapy for locally advanced and recurrent head and neck cancer.
Authors: Celina Chiodo, Sébastien Gros, Brian Lee, Alec Michael Block, Bahman Emami, William Small, Tamer Refaat Abdelrhman
Journal: Journal of Clinical Oncology (2022)

6058 Background: Intraoperative Radiation Therapy (IORT) allows precise delivery of radiation therapy (RT) to a limited target area at high risk of cancer recurrence while minimizing RT to nearby organs at risk. IORT may be particularly beneficial for patients with locally recurrent head and neck cancer (HNC) in a previously irradiated field and for locally advanced HNC cases, in which obtaining negative surgical margins may be difficult. This study aims to present a single institution experience with IORT for HNC patients. Methods: This study included HNC patients treated consecutively with IORT at our institution between 2014 and 2018. Charts were reviewed for patients’ and tumors’ characteristics, IORT technical details, IORT-induced adverse events, and treatment outcomes. Results: The study included 23 eligible patients. Median patient age was 66 (range 33-91). Tumor sites included parotid gland (43%), lymph nodes (43%), oral tongue (9%), and ear (4%). 52% of patients received IORT upfront with or without postoperative adjuvant external beam radiation therapy (EBRT), while 48% received salvage IORT after local tumor recurrence. The median prescribed IORT dose was 7.5 Gy (range 5-14 Gy) in a single fraction prescribed to 5 mm depth with Flat applicators (median diameter of 5 cm). 92% of patients did not experience wound healing complications. One patient (4%) developed postoperative acute thromboembolic stroke, a second patient (4%) experienced protracted wound healing. At a median follow-up of 36 months (range 2-81), 42% of patients presented with no evidence of disease (NED), overall survival was 54%, 13% of patients were alive with disease, and 46% died with disease. Local-regional recurrence rate was 39% (median time to local recurrence was 18 months, range 2-60), rate of distant metastasis was 43% (median time to distant metastasis was 23 months, range 5-60), and 30% of patients had both local-regional recurrence and distant metastases. The percent of local-regional recurrence and distant metastases among patients receiving salvage IORT was 64% and 73% respectively, compared to 23%, and 15% respectively in those receiving upfront IORT with or without adjuvant EBRT. Conclusions: In this single institution chart review study, IORT to locally advanced and recurrent HN cancer patients was a safe treatment modality, with tumor control comparable to historical EBRT data. Larger prospective studies are needed to further assess the utility of IORT in the management of locally advanced and recurrent HN cancer.
A pilot study of trametinib in combination with paclitaxel in the treatment of anaplastic thyroid cancer.
Authors: Eric Jeffrey Sherman, Loren S. Michel, Anuja Kriplani, Lara Dunn, Sofia Haque, Deborah Bang, Sarah Stein, David G. Pfister, Alan Loh Ho
Journal: Journal of Clinical Oncology (2022)

6088 Background: Anaplastic Thyroid Cancer (ATC) is a rare and highly aggressive tumor with extremely poor prognosis. Outside of the recent approval of dabrafenib/trametinib for BRAF mutant tumors, there are no other standard treatment available for metastatic ATC. The majority of ATC is driven through the MAPK pathway. Data in lung cancer suggested synergy with trametinib, a MEK inhibitor, and taxanes. Methods: In this pilot study we used Trametinib (2 mg) daily with Paclitaxel (80 mg/m 2 ) administered weekly for the first 3 weeks out the 4 week-cycle. Restaging imaging was performed every 6-8 weeks (1.5-2 cycles). Eligible patients had ATC with baseline ECOG performance status ≤ 1 and were enrolled at Memorial Sloan Kettering Cancer Center. Prior treatment allowed. Prior brain metastases were allowed if treated and stable off of steroids. Primary objective was PFS at 6 months with the target of &gt; 2 subjects out of 12 at the time point. Results: 12 patients (6 men and 6 women) were enrolled between 11/2017 and 10/2021. Seven (58%) had prior radiation to the neck; 4 (33%) had prior treatment (not including with radiation) for ATC; 1 (8%) had prior brain metastases. Three (25%) partial responses were reported, and five (41.67%) reported stable disease. Subjects with partial responses had a BRAF V600E mutation (1), BRAF fusion gene (1), and a RAS mutation (1). Median time on treatment was 10.5 weeks (3-47+ weeks). Median overall survival was 26 weeks (3-59+). Six-month progression free survival (PFS) was achieved in 3 patient (25%), one of whom remains on study. 2 patients discontinued treatment due to unacceptable toxicity. The most frequent adverse events observed (all grades) were anemia (75%), increased AST, diarrhea and leukopenia (all 50%). Grade 3/4 AEs included neutropenia (25%), with anemia, AST increased, febrile neutropenia, and lymphopenia, all 16.67%. Grade 4 reactions included lymphopenia (n = 2) and leukopenia (n = 1). Conclusions: Our target progression-free survival (PFS) at 6 months was observed on this study. The combination of trametinib and paclitaxel should be evaluated in a larger cohort of patients in the future. Clinical trial information: NCT03085056.
Prognostic factors in sinonasal cancers: A multicenter pooled analysis.
Authors: Alberto Hernando-Calvo, Milica Stefanovic, Shao Hui Huang, Jesús Brenes Castro, Jie Su, Brian O'Sullivan, Jolie Ringash, Alicia Lozano, Beatriz Cirauqui, Ezra Hahn, Iris Teruel, John R de Almeida, Jordi Marruecos, Ian Witterick, Jordi Rubió-Casadevall, David Paul Goldstein, Lillian L. Siu, John Waldron, Anna Spreafico, Marc Oliva
Journal: Journal of Clinical Oncology (2022)

6092 Background: Sinonasal cancers (SC) are heterogeneous diseases. Despite multimodality treatment, overall survival (OS) remains unsatisfactory. We aimed to identify prognostic factors (PFs) associated with patterns of failure and OS in non-metastatic SC (nmSC). Methods: We retrospectively reviewed a pooled dataset of nmSC from Princess Margaret (Canada) and Catalan Institute of Oncology (Spain) treated with definitive surgery ± postop radiotherapy (RT) or RT ± chemo according to institutional protocols between 2010-2019. In squamous cell carcinoma (SCC), HPV status was tested by p16 staining, and HPV DNA (ISH or PCR) if equivocal. The primary goal was to assess the association of tumor histology, stage (by 7 th edition TNM), and other clinicopathological variables on locoregional control (LRC), distant control (DC) and OS. Actuarial rates were calculated with Kaplan–Meier (KM) method. Multivariable analysis (MVA) calculated hazard ratios (aHR) adjusted for histology type, T-/N-categories, and primary treatment. Results: Out of 342 pts, median age was 62 years (y) (range 21-96), Male:Female = 212:130, 95% had ECOG 0-1. Tumor histology types were: 192 (56%) SCC (p16+: 35; p16-/untested: 157), 40 (12%) adenocarcinoma (AD), 33 (10%) sinonasal undifferentiated carcinoma or sinonasal neuroendocrine tumors (SNUC/SNEC), 28 (8%) malignant melanoma (MM), 27 (8%) esthesioneuroblastoma (ES) and 22 (6%) adenoid cystic carcinoma (ACC). Median follow up was 3.6 y (range 0.1-11.3). Three-year actuarial rates for each endpoint are included in table. The PFs for LRC by MVA were: SNUC/SNEC (vs SCC) histology, T3-4 (vs T1-2: aHR 2.4, p = &lt; 0.01) and N+ (vs N-: aHR 1.7, p = 0.02) diseases. The PFs for DC were: MM (vs SCC) and SNUC/SNEC (vs SCC) histology, and T3-4 (vs T1-2: aHR 6.0, p = 0.01) disease. The PFs for OS were: MM (vs SCC) histology, older age (aHR 1.0, p &lt; 0.01), T3-4 (vs T1-2: aHR 5.6, p &lt; 0.01), and N+ (vs N-: aHR 2.5, p &lt; 0.01) disease. There was no difference in primary surgery vs RT in any outcome endpoint (all p &gt; 0.05). p16+ SCC had a marginally higher LRC but similar DC and OS vs p16-/untested SCC (table). Conclusions: This large multicentre cohort of nmSC shows different patterns of relapse and survival with different tumor histologies. Our results suggest that individualization of treatment and follow-up strategies by histologic type is recommended to optimize outcomes in these orphan diseases. [Table: see text]
Nivolumab-based induction chemoimmunotherapy and PD-L1 expression in locoregionally advanced HPV-associated oropharyngeal squamous cell carcinoma.
Authors: Ari Rosenberg, Alexander T. Pearson, Nishant Agrawal, Aditya Juloori, Tanguy Y. Seiwert, Zhen Gooi, Elizabeth A. Blair, Evgeny Izumchenko, Jeffrey Chin, Daniel Ginat, Mark Lingen, Daniel J. Haraf, Everett E. Vokes
Journal: Journal of Clinical Oncology (2022)

6075 Background: Blockade of the PD-1/PD-L1 immune checkpoint improves survival in recurrent/metastatic head and neck cancer. PD-L1 expression is a biomarker that enriches for clinical benefit with anti-PD-1 therapy alone or in combination with chemotherapy in this setting. The role of PD-L1 expression as a predictive biomarker in locoregional human papillomavirus associated (HPV+) head and neck cancer (HNC) treated with induction nivolumab-based chemoimmunotherapy is unknown. We evaluate PD-L1 expression and response to induction chemoimmunotherapy in the context of an investigator initiated trial, OPTIMA II. Methods: Patients with locoregionally advanced HPV+ HNC were enrolled to the prospective OPTIMA II study evaluating induction chemoimmunotherapy followed by response adaptive de-escalated locoregional therapy. Induction therapy consisted of nivolumab, nab-paclitaxel, and carboplatin, for three cycles. Anatomic imaging of the head and neck with either CT or MRI was obtained at baseline and following induction therapy. Expression of PD-L1 was assessed by immunohistochemistry on baseline biopsies and calculation of tumor proportion score (TPS) and combined positive score (CPS) was performed. Response is defined as percentage of tumor shrinkage per RECIST 1.1 criteria. Deep response rate is defined as the proportion of patients with &gt; = 50% tumor shrinkage. Kruskal-Wallis and Mann-Whitney tests were used for analysis. Results: Twenty-nine patients (pts) underwent evaluation of PD-L1 expression and started treatment with induction chemoimmunotherapy. Median age 61 (range 37-81), smoker &gt; 20 pack years in 24%, tonsil primary in 79%, and HPV16 subtype in 97%. The median response following induction was 63% (range 29% to 100%). PD-L1 TPS scores were &lt; 1, 1-19, and &gt; = 20 in 28%, 34%, and 38% respectively. PD-L1 CPS scores were &lt; 20 and &gt; = 20 in 55% and 45% respectively. Median response among PD-L1 TPS of &lt; 1, 1-19, and &gt; = 20 was 49%, 59%, and 66% respectively (p = 0.16). Among PD-L1 CPS of &lt; 20 and &gt; = 20, median response was 57% and 69% respectively (p = 0.11). The deep response rate among PD-L1 CPS &lt; 20 and &gt; = 20 was 69% and 77% respectively. Conclusions: Deep responses were observed following induction chemoimmunotherapy in locoregionally advanced HPV+ HNC. There was a non-significant increase in median response and deep response rate with higher expression of PD-L1. Evaluation of PD-L1 expression as a biomarker for response with induction chemoimmunotherapy is worthy of further investigation in locoregional HPV+ disease. Clinical trial information: NCT03107182.
Quality of life and two-year results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (DO-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer.
Authors: Christopher Nutting, Keith Rooney, Bernadette Foran, Laura Pettit, Matthew Beasley, Laura Finneran, Justin Roe, Justine Tyler, Tom Roques, Audrey Cook, Imran Petkar, Shree Bhide, Devraj Srinivasan, Cheng Boon, Emma De Winton, Robert Frogley, Mark Adrian Sydenham, Marie Emson, Emma Hall
Journal: Journal of Clinical Oncology (2022)

6065 Background: Most newly diagnosed oro- &amp; hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. We investigated if using DO-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Methods: Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary &amp; nodal tumour; 54Gy/30f to remaining pharyngeal subsite &amp; nodal areas at risk of microscopic disease) or DO-IMRT. The volume of the superior &amp; middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in DO-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site &amp; AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT. Secondary endpoints included University of Washington (UW)-Qol, Performance Status Scale Head &amp; Neck (PSS-HN) domain scores (range: 0-100), swallow volume, swallow capacity and local control. Results: 112 patients (56 S-IMRT, 56 DO-IMRT) were randomised from 22 UK &amp; Ireland centres from 06/2016 - 04/2018. 111/112 had RT doses as prescribed (1 patient died before RT). Outcome measures at 12 and 24 months are summarised below. DO-IMRT had higher MDADI scores at 12 (p = 0.04) and 24 (p = 0.07) months. Clinically important improvements in swallowing function were seen in patients receiving DO-IMRT using PSS-HN domains and the UW-QoL tool. Conclusions: DO-IMRT improved patient reported swallowing function compared with S-IMRT. Improvements were seen in overall MDADI as well as functional scores in both PSS-HN and UW-QoL. Clinical trial information: 25458988. [Table: see text]
TPF induction chemotherapy versus PF adjuvant chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicenter, randomized controlled, III trial.
Authors: He Qianyong
Journal: Journal of Clinical Oncology (2022)

6069 Background: To investigate the efficacy and safety of the two modes of concurrent chemoradiotherapy combined with induction or adjuvant chronotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. Methods: A total of 266 patients with locoregionally advanced NPC were enrolled from May 2018 to July 2021 and randomly divided into a test (n = 133) and a control (n = 133) group. In the test group, the docetaxel and cisplatin plus fluorouracil (TPF) regimen was used to induce chronological chemotherapy for 3 cycles (docetaxel 75mg / m2, D1, cisplatin 75mg / m2, d1-d5, fluorouracil 750mg / m2 / D, d1-d5) + 3 cycles of concurrent chemoradiotherapy (cisplatin 100mg / m2; The control group was treated with three cycles of concurrent chemoradiotherapy (cisplatin 100mg / m2) + cisplatin plus fluorouracil (PF) regimen with adjuvant schedule chemotherapy for three cycles (cisplatin 80mg / m2 on days d1-d5, fluorouracil 800mg / m2 / d on days d1-d5). In both groups, intensity-modulated radiation therapy was used with a total dose of 69.96 Gy to the primary tumor at T1 and T2, 72.6 Gy to the primary tumor at T3 and T4, and 69.96 Gy to the positive lymph nodes. Acute adverse effects and survival were compared between the two groups. Results: A median follow-up of 19 months, 129 patients in the test group and 124 in the control group were evaluable for efficacy and adverse effects.Compliance was 96.99% and 90.22%, respectively. The 2-year overall survival rates were 91.7% and 90.5%, and the 2-year progression free survival rates were 92.4% and 90.4% in the test and control groups, respectively, with no significant difference ( P &gt; 0.05). The test group had a lower incidence of radiation mucositis, dry mouth, and dysphagia than the control group ( P &lt; 0.05), whereas the test group had a higher incidence of leukopenia, neutropenia, hemoglobin loss, vomiting ( P &lt; 0.05), decreased radiation dermatitis, platelets There were no significant differences in the categories of creatinine elevation and transaminase elevation (P &gt; 0.05). Conclusions: The patients' compliance was good and the toxic effects such as radiation mucositis, dry mouth and dysphagia were reduced under the treatment mode in which the TPF induced chemotherapy combined with concurrent chemoradiotherapy.Although the toxic effects such as leukopenia, neutropenia, hemoglobin reduction and vomiting were increased, the efficacy was comparable with that of the PF in which the adjuvant schedule chemotherapy combined with concurrent chemoradiotherapy. Clinical trial information: NCT-03574324.
Recombinant human endostatin combined with intensity-modulated radiotherapy in low-risk locoregionally advanced nasopharyngeal carcinoma: A phase II, randomized, multicenter clinical trial.
Authors: Min Kang, Shaomin Lin, Haisheng Zhu, Sihui Liao, Haixin Huang, Bin Yu, Hongqian Wang, Meilian Liu, Jinxian Zhu, Guang Huang, Fen Wang, Tingting Zhang, Zhendong Yang, Pingting Zhou, Ziyan Zhou, Yating Qin, Yutao Qin, Zhuxin Wei, Changhong Zhao, Rensheng Wang
Journal: Journal of Clinical Oncology (2022)

6061 Background: Concurrent chemoradiotherapy (CCRT) is currently considered to be the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), accompanied with non-neglectable toxicity and unsatisfactory compliance. Therefore, it is highly warranted to explore an alternative regimen for LA-NPC. This trial aimed to assess and investigate the efficacy and safety of recombinant human endostatin ( Rh-endostatin) with intensity-modulated radiotherapy (IMRT) for low-risk LA-NPC. Methods: Patients with low-risk LA-NPC were randomly assigned into ERT group (n=60, receiving Rh-endostatin plus radiotherapy) and CCRT group (n=60, receiving cisplatin plus radiotherapy). The primary endpoint was the 5-year overall survival (OS). Non-inferiority was shown if the upper limit of the 95% CI for the difference in 5-year OS between the ERT group and CCRT group did not exceed 15%. The secondary endpoint was 3-year progression-free survival (PFS). Results: A total of 120 patients were included in the trial. After a median follow-up of 71 months (IQR 62-75), the 5-year OS rate was 88.1% in the ERT group and 77.6% in the CCRT group, with a difference of 10.5% (95% CI: -0.03 to 0.24; P non -inferiority = 0.002). Patients in the ERT group had better 3-year PFS than that in the CCRT group (89.8% vs 70.6%; HR = 0.362; 95% CI: 0.150-0.873; P log-rank = 0.018). The overall all-grade toxicity burdens were heavier in CCRT group. No patients died of treatment-related causes. Conclusions: Rh-endostatin combined with IMRT had favorable efficacy, fewer toxic effects and more improved quality of life, which might be a promising alternative regimen to CCRT for low-risk LA-NPC in clinic. Clinical trial information: NCT02237924. [Table: see text]
Cataloging targetable dependencies of head and neck cancer cell lines in the DepMap CRISPR screens.
Authors: Devraj Basu, Austin Cao, Lovely Raghav, Pavithra Rajagopalan, Robert Brody, Phyllis A. Gimotty
Journal: Journal of Clinical Oncology (2022)

6056 Background: The DepMap genome-wide loss of function CRISPR screens offer new insight into gene dependencies in HPV(-) head and neck squamous cell carcinoma (HNSCC) cell lines. We aimed to leverage this data to guide preclinical studies by cataloging targetable dependencies and identifying ones predicted to offer a therapeutic window. We also aimed to identify targets representing potential synthetic lethalities by testing for associations between genetic alterations and dependency profile. Methods: DepMap was queried for gene probability and effect scores in cell lines from 77 tumors, including 62 HPV(-) HNSCCs plus 15 ESCCs, which have comparable etiology, genetic features, and tissue of origin. A probability score of ≥ 0.5 was used as the threshold for essentiality. Essential genes were selected for analysis by 3 criteria: (1) presence in ≥10% cell lines, (2) lack of dependency in CRISPR screens of normal human cell lineages, and (3) designation as druggable by the Drug-Gene Interaction Database. Gene set enrichment analysis was performed using the Hallmark Gene Sets. DepMap gene effect scores were used to prioritize targets likely to have a useful therapeutic window based on median scores greater than for EGFR (0.676), a target with established albeit modest utility for HNSCC. The Open Targets platform was used to identify targets with inhibitors used in trials for other cancers and/or nonmalignant diseases. Associations between dependencies and genetic alterations were defined using two-sample t-tests, with filter conditions of p &lt; 0.05 and effect size ≥1. Results: The 231 genes meeting selection criteria had a median gene effect score of 0.56. The criteria captured targets of standard therapeutic agents including TYMS (5-FU), tubulin genes (paclitaxel), EGFR (cetuximab), plus known oncogenes like PIK3CA. GSEA showed enrichment of known oncogenic signaling pathways including PI3K/AKT and JAK/STAT, as well as hallmark cancer processes like DNA repair and apoptosis. 90% were not known oncogenes cataloged in the OncoKB Database. 45 genes had a median gene effect score between that of EGFR and the median for common essential genes, including 7 without known cancer-promoting roles: OTOP1, DHRSX, UTP11, MBTPS1, SLC25A3, PPIAL4G, and RBM10. 17% had inhibitors that reached a non-HNSCC phase II trial, including 10 targets not previously tested in cancer. Novel associations between dependencies and genetic alterations included DDX3X with NOTCH1mut, ITGB1 with CDKN2Amut, and ATP1A1 with HRASmut. Conclusions: We catalog targetable dependencies in cell line models of HNSCC. While well-studied targets were captured, many genes lacked known roles in malignancy. Targets of inhibitors tested in other diseases provide new tools to guide preclinical studies. Association of some dependencies with known molecular subgroups in HNSCC may enhance use of cell line models to personalize therapy.